How an Epithelial Cell Swells Is a Determinant of the Signaling Pathways that Activate RVD

How does a cell sense changes in volume and transduce those signals into a regulatory response? Several recent reviews have implicated known second messengers, such as Ca²⁺, phosphoinositides, membrane stretch, cytoskeletal changes, changes in intracellular pH (pH_i), cytosolic ionic strength or protein content as transducing mechanisms. This chapter focuses on studies which suggest that the regulation of K⁺ and Cl^– channel activation in jejunal villus enterocytes is dependent on both the extent of cell swelling, as well as the mechanism by which cell volume is increased. The first evidence that different signaling mechanisms were responsible for activation of the RVD conductive pathways following hypotonic or Na+-nutrient swelling came from volume experiments using protein kinase C inhibitors. The results of the studies described in the chapter suggest that the mode of cell swelling determines the nature of the signaling pathways that are responsible for activating volume regulatory K⁺ and Cl^- conductances.